CIRCULATORY AND METABOLIC EFFECTS OF BETA-ADRENERGIC-BLOCKADE IN THE HYPERINSULINEMIC OVINE FETUS

Offspring of women with poorly controlled diabetes exhibit hypoxemia, elevated catecholamine concentration at birth, and an increased incide nce of fetal death. Experimental fetal hyperinsulinemia results in inc reased catecholamine concentration and hemodynamic changes including i ncreased combined ventricular output and vasodilation of select fetal organs. We hypothesized that insulin-induced catecholamine-mediated be ta-adrenergic stimulation supports some of these hemodynamic changes i n the hyperinsulinemic ovine fetus. To study this, 24 chronically inst rumented fetal sheep receiving insulin for 24 h were exposed to beta-( propranolol), beta1- (metoprolol), and beta2- (ICI 118,551) adrenergic blockade. Insulin infusion resulted in hyperinsulinemic-hypoglycemia, a surge in epinephrine and norepinephrine concentration, and increase s in the combined ventricular output and regional blood flow to the he art, adrenal glands, kidney, gastrointestinal tract, liver, fat, muscl e, carcass, and placenta. In the hyperinsulinemic state, beta-adrenerg ic blockade was associated with significant reductions in the combined ventricular output and blood flow to fat, carcass, lungs, and the pla centa; beta1-blockade was associated with reductions in the combined v entricular output and blood flow to the lungs; and beta2-adrenergic bl ockade was associated with reductions in blood flow to muscle and lung s. Because beta-adrenergic blockade was associated with reductions in placental blood flow during hyperinsulinemia, oxygen and glucose metab olism were also compromised. We conclude that in the hyperinsulinemic- hypoglycemic normoxemic ovine fetus, insulin-induced catecholamine-med iated hemodynamic changes are modulated in part by beta-adrenergic rec eptor stimulation.